N-methyl-D-aspartate (NMDA) receptors are prevalent in the brain and are activated by excitatory amino acids, e g. glutamate and aspartate.
Several non-competitive NMDA receptor antagonists are known. (A non-competitive receptor antagonist is a compound that decreases the potency of an agonist, but whose antagonism cannot be overcome entirely by increasing agonist dosage.) Examples of non-competitive NMDA receptor antagonists are phencyclidine, which is commonly referred to as "PCP" or "angel dust," the PCP analog 1-[1-(2-thienyl)-cyclohexyl]-piperidine, which is commonly referred to as "TCP", and the compound 5-methyl-10,11-dihydro-5H-dibenzo [a,d] cycloheptene-5,10-imine, which is commonly referred to as "MK-801"; see U.S. Pat. No. 4,399,141.
Non-competitive NMDA receptor antagonists are useful for treating or preventing neuronal cell loss associated with stroke, ischemia, CNS trauma, hypoxia and hypoglycemia, as well as neurodegenerative diseases including Alzheimer's disease, amyotrophic lateral sclerosis, Huntington's disease and Down's syndrome. See J. A. Kemp et al., Non-competitive Antagonists of Excitatory Amino Acid Receptors, TINS, Vol. 10, No. 7, 294-298 (1987).